Effects of niludipine (Bay-a-7168) on transmembrane action potentials of rabbit sinus node cells and atrial muscle fibers.

Effects of niludipine (bis(2-propoxyethyl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedic arboxylate; Bay-a-7168) on isolated rabbit sinus node and right atrial preparations were studied using intracellular microelectrode techniques. Niludipine in concentrations above 1 X 10(-8) M caused dose-dependent changes in the membrane action potentials of the preparations. In spontaneously firing sinus node cells, a marked decrease in the amplitude (AMP) and maximum rate of depolarization (MRD) of action potentials as well as a slight decrease in their maximum diastolic potential (MDP) were observed after drug administration. In constantly driven atrial muscle fibers, the early repolarizing phase was accelerated (shortening of action potential duration) and AMP was decreased by several millivolts. However, little change occurred in the MDP and MRD of atrial muscle fibers even at the highest concentration (1 X 10(-6) M). Niludipine prolonged the effective refractory period of atrial muscle fibers by 4--8 msec. At the same time, it caused a marked decrease in the amplitude of the premature action potentials and prolonged their propagation time. Most of these effects of niludipine, which may be attributed to the reduction of the slow inward current through the myocardial cell membrane, were antagonized by the concomitant administration of isoproterenol (1 X 10(-6) M).